Prediction and evaluation of protein-protein interaction in keratinocyte differentiation.
Terminal differentiation of skin keratinocytes is a vertically directed multi-step process that is tightly controlled by the sequential expression of a variety of genes. We previously investigated the gene expression profile and found that many of differentiation-related genes expressed in a temporally regulated manner. In this study, we attempted to find the hub-molecules and their intracellular signaling networks during keratinocyte differentiation using in silico analysis of data obtained from previous studies. We used protein-protein interaction prediction software called PSIMAP, and drew a hypothetical signaling network. We chose one candidate hub-molecule SHC1 that were predicted to link EGFR and MAPK signal, and then evaluated the protein-protein interactions experimentally. As predicted, SHC1 bound to the MEK1 in an EGF-regulated manner. Furthermore, SHC1 bound to the MEK1 and p38 MAPK in a keratinocyte differentiation dependent manner. These results demonstrate that in silico protein-protein interaction prediction system can be used to efficiently and cost-effectively select the experimental candidates.
Yoon
Hyun Kyung
HK
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, 55 Munhwa-ro, Daejeon 301-747, Republic of Korea; School of Bioscience and Biotechnology, Chungnam National University, Daejeon, Republic of Korea.
Sohn
Kyung-Cheol
KC
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, 55 Munhwa-ro, Daejeon 301-747, Republic of Korea.
Lee
Jung-Suk
JS
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, 55 Munhwa-ro, Daejeon 301-747, Republic of Korea.
Kim
Yu Jin
YJ
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, 55 Munhwa-ro, Daejeon 301-747, Republic of Korea.
Bhak
Jong
J
The Korea BioInformation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
Yang
Jun-Mo
JM
Department of Dermatology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea.
You
Kwan-Hee
KH
School of Bioscience and Biotechnology, Chungnam National University, Daejeon, Republic of Korea.
Kim
Chang-Deok
CD
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, 55 Munhwa-ro, Daejeon 301-747, Republic of Korea. Electronic address: cdkimd@cnu.ac.kr.
Lee
Jeung-Hoon
JH
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, 55 Munhwa-ro, Daejeon 301-747, Republic of Korea. Electronic address: jhoon@cnu.ac.kr.
D001709:Biotechnology; D002454:Cell Differentiation; D019295:Computational Biology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction; D012984:Software
D011506:Proteins